The objective of this project is to increase our knowledge of the mechanisms controlling ionic conductance of neuronal postsynaptic membranes. The particular aims of this grant period are; a, to establish the nature of the rate limiting step controlling EPSC decay and b, to obtain estimates of mean single channel conductance. In brief, the proposed work will involve the following experiments: 1. Experiments will be initiated to determine the influence of membrane voltage and temperature on the kinetics of EPSC decay and acetylcholine-induced current fluctuations and on mean single channel conductance. 2. Experiments will be undertaken to analyze the alteration of EPSC decay by procaine and other pharmacological blocking agents. Preliminary results indicate that atropine in high concentration produced local anesthetic-like changes in the EPSC decay time course. In the presence of 10 to the minus 5th power - 10 to the minus 4th power M atropine the decay time course became complex with the initial exponential component of decay faster and the final component of decay slower than the decay tau observed in untreated cells. These observations are consistent with a model of drug action in which the antagonist blocks open postsynaptic channels. The action of atropine will be compared with that of procaine. These experiments will involve a detailed kinetic analysis of the alteration in EPSC decay and power spectrum of acetylcholine-induced current fluctuations.